Oncology Research最新文献

{"title":"Mitochondrial pyruvate dehydrogenase phosphatase metabolism disorder in malignant tumors.","authors":"Yufeng Wang, Huifeng Dang, Qianqian Wang, Shuxiao Wu, Lei Han, X U Luo, Yingxia Tian, Hailin Tang","doi":"10.32604/or.2025.063716","DOIUrl":"10.32604/or.2025.063716","url":null,"abstract":"<p><p>This review focuses on the metabolic issues related to mitochondrial pyruvate dehydrogenase phosphatase (PDP) in malignant tumors and its potential mechanisms. Recent research on tumor metabolic mechanisms has shown that PDP dysregulation is closely linked to metabolic reprogramming in tumor cells, and potentially promotes tumor. Research has comprehensively explored the structural-functional characteristics of PDP, its metabolic regulatory mechanisms, and its role in various types of malignant tumors. Nevertheless, several questions still exist regarding its potential mechanisms within acetylation, phosphorylation, hypoxia, immune infiltration, mitochondrial metabolism, drug resistance, oxidative phosphorylation, and tumor prognosis. This article intends to summarize the latest research, examine PDP's potential as a therapeutic target, and propose future research directions to enhance cancer treatment strategies.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1861-1874"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Inhibition of Liver Carcinoma Cell Invasion and Metastasis by Knockdown of Cullin7 <i>In Vitro</i> and <i>In Vivo</i>.","authors":"","doi":"10.32604/or.2025.070134","DOIUrl":"https://doi.org/10.32604/or.2025.070134","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3727/096504016X14519995067562.].</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2179"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying ATP-Binding Cassette Member B5 as a New Biomarker for Oral Squamous Cell Carcinoma.","authors":"Li Yu, Xiaoyan Zhang, Yan Feng, Xinyue Liao, Tiejun Zhou, Hang Si, Yun Feng, Decai Wang, Yongxian Lai","doi":"10.32604/or.2025.064276","DOIUrl":"10.32604/or.2025.064276","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a low five-year survival rate. ATP-binding cassette subfamily B member 5 (ABCB5) has been linked to tumorigenesis. However, its role in inducing OSCC remains unclear.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot, and immunocytochemistry (ICC) were performed to examine the level of ABCB5 in OSCC (CAL27 and HSC-3) and human oral keratinocyte (HOK). ABCB5 was knocked down in CAL27 cells using ABCB5-specific small interfering RNA (ABCB5 siRNA), and its contribution to migration, invasion, and epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose their tight junction and acquire an increased migratory and invasive phenotype resembling that of mesenchymal cells, were evaluated by three-dimension and transwell migration and invasion assays, qRT-PCR and ICC. An <i>in vivo</i> OSCC model was established using 4-nitroquinoline-1-oxide (4NQO), a carcinogenic chemical that is commonly used to develop OSCC by destroying DNA synthesis and oxidative stress. Pathological alterations, ABCB5, and EMT markers were evaluated by H&E staining, immunohistochemistry, and qRT-PCR.</p><p><strong>Results: </strong>ABCB5 was significantly upregulated in CAL27 and HSC-3 cells as compared to HOK. Knockdown of ABCB5 significantly reduced the number of migrated and invaded CAL27 cells, accompanied by the significantly increased E-cadherin and decreased Vimentin and N-cadherin under Transforming growth factor β (TGF-β) treatment. <i>In vivo</i>, as OSCC advanced, a notable rise in the expressions of ABCB5, N-cadherin, and Vimentin, while a statistical decrease in E-cadherin was demonstrated.</p><p><strong>Conclusion: </strong>ABCB5 promotes the migration, invasion, and EMT of OSCC. ABCB5 might be a new biomarker and potential therapeutic target for OSCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2037-2053"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VPS37A Activates the Autophagy-Lysosomal Pathway for TNFR1 Degradation and Induces NF-<b>κ</b>B-Regulated Cell Death under Metabolic Stress in Colorectal Cancer.","authors":"Chuncheng Liu, Xiaohan Liu, Ziqi Li, Yanruoxue Wei, Bangdong Liu, Peng Zhu, Yukun Liu, Ran Zhao","doi":"10.32604/or.2025.065739","DOIUrl":"10.32604/or.2025.065739","url":null,"abstract":"<p><strong>Background: </strong>VPS37A (VPS37A subunit of ESCRT-I), a component of the ESCRT-I (endosomal sorting complex required for transport I) complex, mediates vesicular trafficking through sorting endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Although accumulating evidence indicates that VPS37A deficiency occurs in numerous malignancies and exerts tumor-suppressive effects during cancer progression, its functional significance in colorectal cancer (CRC) pathogenesis remains poorly characterized. Therefore, this study aims to further investigate the functional and molecular mechanisms by which VPS37A downregulation contributes to malignant biological phenotypes in CRC, with a specific focus on how its dysregulation affects cell death pathways.</p><p><strong>Methods: </strong>Multi-omics analysis of TCGA, GEO, and CPTAC cohorts identified VPS37A as a downregulated tumor suppressor gene in CRC. The prognostic relevance of VPS37A was validated in two clinical cohorts (Cohorts 1 and 2) using immunohistochemistry. Functional assays in VPS37A-overexpressing CRC cells and xenografts assessed proliferation, cell cycle progression, and stress-induced cell death. RNA sequencing, nuclear factor kappa-B (NF-κB) luciferase reporter assays, and lysosomal inhibition experiments elucidated the mechanisms underlying tumor necrosis factor receptor 1 (TNFR1) degradation.</p><p><strong>Results: </strong>VPS37A is significantly downregulated in advanced-stage CRC and independently predicts poor survival. Functionally, VPS37A overexpression suppresses proliferation and induces G2/M arrest <i>in vitro</i>, while reducing xenograft growth. Under metabolic stress (glucose deprivation/galactose adaptation), VPS37A triggers cell death via apoptosis, necroptosis, and ferroptosis. Mechanistically, VPS37A redirects TNFR1 to lysosomal degradation, suppressing NF-κB nuclear translocation and transcriptional activity.</p><p><strong>Conclusion: </strong>VPS37A deficiency drives CRC progression by sustaining TNFR1/NF-κB signaling under metabolic stress. Restoring VPS37A activity promotes TNFR1 degradation, offering a therapeutic strategy to counteract NF-κB-mediated treatment resistance in CRC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2085-2105"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Molecular Subtypes and Prognostic Features for Triple-Negative Breast Cancer Based on Golgi Apparatus-Related Gene Signature.","authors":"Zhun Yu, Jie Wang, Guoping Xu","doi":"10.32604/or.2025.061757","DOIUrl":"10.32604/or.2025.061757","url":null,"abstract":"<p><p><b>Objectives:</b> Triple-negative breast cancer (TNBC) presents a major treatment challenge due to its aggressive behavior. The dysfunction of the Golgi apparatus (GA) contributes to the development of various cancers. This study aimed to utilize GA-related genes (GARGs) to forecast the prognosis and immune profile of TNBC. <b>Methods:</b> The data were downloaded from The Cancer Genome Atlas (TCGA) database, including 175 TNBC and 99 healthy samples. The differentially expressed GARGs (DEGARGs) were analyzed using the TCGA biolinks package. The patients with TNBC were classified into two clusters utilizing the ConsensusClusterPlus package according to prognosis-related DEGARGs, followed by comparing the differences in prognosis and immune infiltration between the two clusters. Next, LASSO and stepwise Cox regression were applied to establish a GARGs signature to forecast the TNBC prognosis. The association of the GARGs signature with immune infiltrates and drug sensitivity was further explored. <b>Results:</b> In total, 430 DEGARGs were identified between TNBC and healthy samples, among which 20 were related to TNBC prognosis. Two GARG-related molecular clusters associated with different survival times and immune heterogeneity were identified. A risk model for TNBC was established based on six GARGs, and the high-risk (HR) group exhibited a poor prognosis. The HR group demonstrated a distinctly high M2 macrophage infiltration and low M1 macrophage infiltration, which contributed to an immunosuppressive tumor microenvironment and thus led to poor prognosis of the HR group. Immune dysfunction scores and programmed cell death ligand 1 (PD-L1) expression were substantially elevated in the HR group. The HR group showed increased sensitivity to anticancer drugs, such as cisplatin. <b>Conclusion:</b> Our findings suggest that GARGs are involved in the pathogenesis of TNBC and provide new insights into prognostic prediction. The identified clusters and GARGs signatures have the potential to guide individualized therapy.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2013-2035"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Stemness-Associated Scores: Enhancing Predictions of Hepatocellular Carcinoma Prognosis and Tumor Immune Microenvironment.","authors":"Gaofeng Pan, Jiali Li, Weijie Sun, Jiayu He, Maoying Fu, Yufeng Gao","doi":"10.32604/or.2025.063993","DOIUrl":"10.32604/or.2025.063993","url":null,"abstract":"<p><strong>Aims: </strong>The aim of this study is to develop a prognostic model for hepatocellular carcinoma (HCC) using stemness-related genes (SRGs), while also pinpointing and validating pivotal genes associated with this process.</p><p><strong>Methods: </strong>Utilizing the TCGA and ICGC database, a prognostic stemness-related scores (SRS) for HCC through a combination of WGCNA and machine learning. Bioinformatics analysis evaluated tumor immune infiltration characteristics and drug sensitivity in different SRS subgroups, identifying the key gene TOMM40L. qRT-PCR and IHC were employed to detect the expression level of TOMM40 L. Kaplan-Meier survival analysis assessed the prognostic value of TOMM40L in HCC. <i>In vitro</i> cell experiments explored the influence of TOMM40L on HCC cell progression and stemness.</p><p><strong>Results: </strong>The prognostic model SRS for HCC was developed and validated, incorporating four SRGs: EIF2B4, CDCA8, TCOF1, and TOMM40L. Distinct variations in tumor immune infiltration profiles and drug sensitivity were noted across different SRS subgroups. Elevated TOMM40L levels are notably detected in malignant tissues in contrast to adjacent tissues, with heightened TOMM40L expression correlating with unfavorable prognostic outcomes. In addition, knockdown of TOMM40L significantly inhibited cell progression and stemness. <b>Conclusion:</b> The newly constructed SRS model is a potential biomarker for assessing HCC prognosis, and the key gene TOMM40L exhibits oncogenic properties.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1991-2011"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CYMP-AS1 Promotes Ovarian Cancer Progression by Enhancing the Intracellular Translocation of hnRNPM and Reducing the Stability of AXIN2 mRNA.","authors":"Yuhan Wang, Yimei Meng, Wanqiu Xia, Yusen Liang, Yaru Wang, Peiling Li, Lei Fang","doi":"10.32604/or.2025.064367","DOIUrl":"10.32604/or.2025.064367","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is a representative malignancy of the female reproductive system, with a poor prognosis. Long non-coding RNAs (lncRNAs) crucially affect tumor development. This study aimed to identify lncRNAs that potentially participated in OC.</p><p><strong>Methods: </strong>LncRNA expression in cells and tissues was quantified using reverse transcription-quantitative PCR, while fluorescence <i>in situ</i> hybridization determined their cellular localization. Various <i>in vitro</i> assays, together with a mouse xenograft model, were employed to elucidate the function of CYMP antisense RNA 1 (CYMP-AS1) in OC. The molecular mechanisms underlying CYMP-AS1 regulation were investigated through RNA pull-down and immunoprecipitation assays, immunofluorescence staining, western blotting, and mRNA stability assays.</p><p><strong>Results: </strong>This study identified a previously unreported lncRNA, CYMP-AS1, which exhibits increased expression in the cytoplasm of OC tissues and cells. Knockout of CYMP-AS1 reduced the OC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). CYMP-AS1 directly interacts with heterogeneous nuclear ribonucleoprotein M (hnRNPM), inducing its intracellular translocation and reducing the stability of Axis inhibition protein 2 (AXIN2) mRNA. This process ultimately elevated the expression of Wnt/β-catenin signaling pathway-related proteins.</p><p><strong>Conclusion: </strong>This study confirms CYMP-AS1 as a novel biomarker in OC progression and suggests that the CYMP-AS1/hnRNPM/AXIN2 axis may offer an innovative strategy for OC treatment.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2141-2159"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated PI3K/AKT signaling in oral squamous cell carcinoma: The tumor microenvironment and epigenetic modifiers as key drivers.","authors":"Vinothkumar Veerasamy, Veeravarmal Veeran, Siddavaram Nagini","doi":"10.32604/or.2025.064010","DOIUrl":"10.32604/or.2025.064010","url":null,"abstract":"<p><p>The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway is one of the most frequently dysregulated signaling networks in oral squamous cell carcinoma (OSCC). Although the tumor microenvironment (TME) and epigenetic modifiers are recognized to play a pivotal role in aberrant activation of the PI3K/AKT pathway in OSCC, the available evidence is fragmentary and a comprehensive analysis is warranted. This review evaluates the intricate mechanisms by which various components of the TME facilitate proliferation, apoptosis evasion, invasion, migration, angiogenesis, metastasis, as well as therapy resistance in OSCC through activation of PI3K/AKT signalling. The review has also analysed how epigenetic modifiers such as DNA methylation, histone modifications, and noncoding RNAs that have emerged as key players in orchestrating OSCC development and progression influence the PI3K/AKT pathway. Preclinical studies and clinical trials on the efficacy of PI3K/AKT inhibitors as viable options for OSCC treatment are discussed. Overall, this review supports the tenet that the PI3K/AKT pathway, which functions as a central hub through crosstalk with several oncogenic signaling pathways and overarching impact on all the hallmark traits of cancer, offers immense potential as a biomarker and oncotherapeutic target for OSCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1835-1860"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPX4 predicts poor prognosis and regulates tumor proliferation and senescence in colorectal adenocarcinoma.","authors":"Y U Zhang, Qingkun Wang, Yue Han, Junjie Piao, Xiuying Jin","doi":"10.32604/or.2025.063395","DOIUrl":"10.32604/or.2025.063395","url":null,"abstract":"<p><strong>Background: </strong>Colorectal adenocarcinoma (COAD) is one of the most common gastrointestinal malignancies. There is a pressing need to recognize reliable biomarkers that can improve diagnostic accuracy, predict prognosis, and serve as effective molecular targets. Glutathione peroxidase 4 (GPX4) is an important antioxidant protein. Evidence demonstrates that abnormal expression of GPX4 is related to cancer initiation and progression. However, the role of GPX4 in COAD remains unclear.</p><p><strong>Methods: </strong>We employed bioinformatics analysis and conducted subsequent validation of biological processes, including cell counting kit-8 assay (CCK-8), colony formation assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), 5-ethynyl-2'-deoxyuridine assay (EdU), western blot, immunohistochemistry, senescence associated β-galactosidase (SA-β-gal) staining and immunofluorescence to explore the expression status, prognostic value and biological function of GPX4 in COAD.</p><p><strong>Results: </strong>Our data revealed that GPX4 mRNA expression was upregulated in COAD tissues and could predict the prognosis in patients with COAD. High GPX4 expression was associated with increased infiltration of malignant cells. We also performed a series of cell experiments confirming that GPX4 knockdown inhibited proliferation and induced cellular senescence, as determined by using CCK-8, colony formation, and EdU assay. In addition, SA-β-gal staining and senescence-associated secretory phenotype (SASP) components, such as P21 and Interleukin-6 (IL-6), were increased in GPX4 knockdown cells, while Lamin B1 was decreased. Moreover, we predicted that high expression of GPX4 was related to low immune cell infiltration.</p><p><strong>Conclusion: </strong>This study demonstrates that GPX4 is a potential prognostic biomarker and target gene for COAD.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"1933-1945"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OTUD7B Stabilization by METTL14-Mediated m6A Methylation Drives HIF-1<b>α</b> Expression in Esophageal Squamous Cell Carcinoma.","authors":"Fei Ren, Yansen Cai, Yang Song","doi":"10.32604/or.2025.061301","DOIUrl":"10.32604/or.2025.061301","url":null,"abstract":"<p><strong>Objectives: </strong>Epigenetic changes, particularly N6-methyladenosine (m6A) modifications, play a pivotal role in cancer development. This study explored the role of ovarian tumor deubiquitinase 7B (OTUD7B) in esophageal squamous cell carcinoma (ESCC) in the context of m6A methylation and the hypoxia-inducible factor-1α (HIF-1α) pathway.</p><p><strong>Methods: </strong>The GSE179267 dataset was used to conduct differential gene expression analysis to identify key m6A-enriched genes. The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Sequence-based RNA Adenosine Methylation Site Predictor (SRAMP) databases were used to evaluate the expression of OTUD7B in ESCC and its correlation with methyltransferase-like 14 (METTL14) and HIF-1α. The m6A content in total RNA extracted from ESCC cells was assessed using a dot blot assay. Gene-specific m6A-PCR was used to quantify m6A modifications in OTUD7B mRNA. The functional role of OTUD7B was explored using clonogenic and Transwell assays. The effect of OTUD7B on HIF-1α ubiquitination was detected using a co-immunoprecipitation assay.</p><p><strong>Results: </strong>OTUD7B was identified as a pivotal m6A-driven oncogene correlated with METTL14 and HIF-1α. METTL14 enhanced the mRNA stability and expression of OTUD7B through m6A methylation. OTUD7B overexpression counteracted the inhibitory effects of METTL14 knockdown on cell proliferation and invasion and stabilized HIF-1α by promoting deubiquitination.</p><p><strong>Conclusion: </strong>METTL14 plays a crucial role in the stabilization of OTUD7B through m6A methylation, thereby inhibiting the ubiquitin-proteasomal degradation of HIF-1α in ESCC. These findings highlight the potential of targeting the METTL14-OTUD7B axis as a therapeutic strategy for ESCC.</p>","PeriodicalId":19537,"journal":{"name":"Oncology Research","volume":"33 8","pages":"2055-2074"},"PeriodicalIF":4.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}